Evidence map›Paper›PMID 36566259›Full record

ArticleNature communications2022

A genome-wide CRISPR screen identifies WDFY3 as a regulator of macrophage efferocytosis.

Jianting Shi, Xun Wu, Ziyi Wang, Fang Li, Yujiao Meng, Rebecca M Moore, Jian Cui, Chenyi Xue, Katherine R Croce, Arif Yurdagul and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 47 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. STAT4-dependent regulation of neuroinflammation in atherosclerosis.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. DietaryInternational journal of molecular sciences · 2025
    Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Frontiers in genetics · 2025
    Article
  18. Article
  19. Efferocytosis in atherosclerosis.Nature reviews. Cardiology · 2024
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 7 institutions in 2 countries.

Jianting Shi *Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0003-1558-7791
Xun Wu *Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Ziyi WangCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Fang LiCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Yujiao MengCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Rebecca M MooreCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Jian CuiCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Chenyi XueCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
Katherine R CroceDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Arif YurdagulDepartment of Molecular & Cellular Physiology, Louisiana State University Health Sciences Center at Shreveport, Shreveport, LA, USA.
John G DoenchBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-3707-9889
Wei LiCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Konstantinos S ZarbalisUniversity of California at Davis, Department of Pathology and Laboratory Medicine, Sacramento, CA, 95817, USA.ORCID 0000-0003-0681-2707
Ira TabasDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Ai YamamotoDepartment of Pathology and Cell Biology, Columbia University, New York, NY, USA.
Hanrui ZhangCardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA. hz2418@cumc.columbia.edu.ORCID 0000-0001-8655-938X
Columbia University Irving Medical Center · USColumbia University · USBeijing University of Chinese Medicine · CNBroad Institute · USChildren's National · USLouisiana State University Health Sciences Center Shreveport · USShriners Hospitals for Children - Northern California · US

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Parisa Tehranifar · 1985 to 2026
$115.3M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Translational Biomarker Analytical Core (TBAC)P30DK063608 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI DOMENICO ACCILI · 2003 to 2026
$36.7M
The Physical Biology of Neurodegeneration in Sporadic Amyotrophic Lateral Sclerosis/Frontotemporal DementiaR01NS127186 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOLT, LIAM J, PHATNANI, HEMALI · 2021 to 2025
$8.2M
A Mechanistic and Translational Research Program Linking Impaired Resolution, Defective Efferocytosis, and Clonal Hematopoiesis to the Formation of Clinically Dangerous Atherosclerotic PlaquesR35HL145228 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TABAS, IRA A · 2019 to 2025
$6.8M
Modulating selective autophagy to modify Huntington's diseaseR01NS077111 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Ai Yamamoto · 2012 to 2026
$4.3M
Selective autophagy in Parkinson'sdiseaseR01NS101663 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Ai Yamamoto · 2018 to 2026
$3.1M
Discovering Wdfy3 as a novel regulator of macrophage efferocytosis by genome-wide CRISPR screenR01HL151611 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, HANRUI · 2020 to 2024
$3.0M
Processing of Apoptotic Cell-Derived Cargo by Macrophages Continues Efferocytosis and Drives Atherosclerosis RegressionR00HL145131 · NHLBI · LOUISIANA STATE UNIV HSC SHREVEPORT · PI YURDAGUL, ARIF · 2021 to 2023
$747k
Macrophage-specific function of GWAS CAD-associated LIPA alleles in atherosclerosisR00HL130574 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ZHANG, HANRUI · 2018 to 2020
$733k
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
Mosaic analysis with double markers in the study of neuronal migration disordersR21MH115347 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI ZARBALIS, KONSTANTINOS · 2018 to 2019
$432k
NCATS NIH HHS UL1 TR001873NCI NIH HHS P30 CA013696NCRR NIH HHS S10 RR027050NHLBI NIH HHS R00 HL130574NHLBI NIH HHS R00 HL145131NHLBI NIH HHS R01 HL151611NHLBI NIH HHS R35 HL145228NIDDK NIH HHS P30 DK063608NIH HHS S10 OD019973NIH HHS S10 OD020056NIMH NIH HHS R21 MH115347NINDS NIH HHS R01 NS077111NINDS NIH HHS R01 NS101663NINDS NIH HHS R01 NS127186
6 · The paper itself

Abstract

Phagocytic clearance of dying cells, termed efferocytosis, is essential for maintaining tissue homeostasis, yet our understanding of efferocytosis regulation remains incomplete. Here we perform a FACS-based, genome-wide CRISPR knockout screen in primary mouse macrophages to search for novel regulators of efferocytosis. The results show that Wdfy3 knockout in macrophages specifically impairs uptake, but not binding, of apoptotic cells due to defective actin disassembly. Additionally, WDFY3 interacts with GABARAP, thus facilitating LC3 lipidation and subsequent lysosomal acidification to permit the degradation of apoptotic cell components. Mechanistically, while the C-terminus of WDFY3 is sufficient to rescue the impaired degradation induced by Wdfy3 knockout, full-length WDFY3 is required to reconstitute the uptake of apoptotic cells. Finally, WDFY3 is also required for efficient efferocytosis in vivo in mice and in vitro in primary human macrophages. This work thus expands our knowledge of the mechanisms of macrophage efferocytosis, as well as supports genome-wide CRISPR screen as a platform for interrogating complex functional phenotypes in primary macrophages.

Indexed as

Adaptor Proteins, Signal TransducingAutophagy-Related ProteinsClustered Regularly Interspaced Short Palindromic RepeatsMacrophagesPhagocytosisAnimalsApoptosisCells, CulturedHumansMiceMice, Inbred C57BLAdaptor Proteins, Signal TransducingAutophagy-Related ProteinsWDFY3 protein, humanWdfy3 protein, mouse

Identifiers

PMID36566259
PMCPMC9789999
OpenAlexW4312118929

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.